Antibodies against adhesion molecules reduce apoptosis after transient middle cerebral artery occlusion in rat brain
Antibodies against adhesion molecules reduce apoptosis after transient middle cerebral artery occlusion in rat brain
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DOI：
10.1097/00004647-199607000-00007
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发表时间：
1996-07-01
影响因子：
6.3
通讯作者：
Prostak, J
中科院分区：
文献类型：
--
作者：
Chopp, M;Li, Y;Prostak, J
我们检验了用抗粘附分子抗体治疗大鼠短暂局灶性脑缺血减少细胞凋亡的假设。通过将尼龙单丝插入颈内动脉，使大鼠（n = 31）经受大脑中动脉（MCA）闭塞2小时。在再灌注时，用针对细胞间粘附分子（ICAM）-1）（n = 8）或整合素CD 11b/CD 18（n = 10）的单克隆抗体处理动物，或给予IgG 1作为对照（n = 13）。在缺血后48小时，处死动物，并使用苏木精和伊红（H/E）分析脑缺血性细胞损伤;使用末端脱氧核苷酸转移酶（TdT）介导的dUTP-生物素缺口末端标记（TUNEL）方法分析细胞凋亡;使用抗髓过氧化物酶（MPO）抗体免疫组织化学分析炎性细胞。数据显示，与对照动物相比，用抗ICAM-1和抗CD 11b抗体处理的两种动物中梗死体积显著减少（p <0.01），凋亡细胞的绝对数量下降（p <0.001），并且凋亡细胞的数量标准化（相对于缺血区域，p < 0.05）。与对照组相比，治疗组MPO免疫反应阳性细胞数也减少（p < 0.05）。这些数据表明，用抗粘附分子抗体治疗选择性地减少凋亡，并且抗体治疗减少缺血性细胞损伤的有益效果的贡献因素可能是凋亡细胞数量的减少。
We tested the hypothesis that treatment of transient focal cerebral ischemia in rat with antibodies directed against adhesion molecules reduces apoptosis. Rats (n = 31) were subjected to 2 h of middle cerebral artery (MCA) occlusion induced by intraluminal insertion of a nylon monofilament into the internal carotid artery, Upon reperfusion, animals were treated with monoclonal antibodies directed against intercellular adhesion molecule (ICAM)-1) (n = 8) or integrin CD11b/CD18 (n = 10), or administered IgG1 as a control (n = 13). At 48 h after ischemia, animals were killed and the brains analyzed for ischemic cell damage, using hematoxylin and eosin (H/E); apoptosis, using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) method; and inflammatory cells, using immunohistochemistry with an anti-myeloperoxidase (MPO) antibody. Data revealed a significant reduction in the volume of infarction (p < 0.01) and a decline in the absolute (p < 0.001), and normalized (to the ischemic area, p < 0.05) numbers of apoptotic cells in both animals treated with anti-ICAM-1 and anti-CD11b antibodies compared to control animals. The numbers of immunoreactive MPO cells were also reduced in the treatment groups compared to those in the control group (p < 0.05). These data suggest that treatment with anti-adhesion molecule antibodies selectively reduce apoptosis, and that a contributing factor to the beneficial effect of antibody treatment for reducing ischemic cell damage may be a reduction in numbers of apoptotic cells.